tbuckley/cabot-search huggingface dataset:
Abstract 13514: Associations Between Plasma Metabolites With Body Composition Traits and Their Responses to Exercise Training
Authors: Prasun Dev, Jacob L Barber, William A Clarkson, Jeremy M Robbins, Prashant Rao, Michael Mi, Sujoy Ghosh, Daniel H Katz, Clary Clish, Claude Bouchard, Robert E Gerszten, Mark A Sarzynski
Journal: Circulation (2022)

INTRODUCTION: Although exercise training can improve body composition, the molecular biomarkers and mechanisms related to these changes have not been fully elucidated. HYPOTHESIS: We hypothesized that distinct metabolite signatures exist for both baseline levels and exercise responsiveness of body composition traits, with substantial overlap across traits. METHODS: Measurements were taken before and after 20 weeks of endurance training in self-identified Black and White adults of the HERITAGE Family Study (n=652). 300 targeted plasma metabolites were measured using LC-MS. Underwater weighing, CT scans, and anthropometric measurements were used to derive the 11 body composition traits included in this study: BMI, body surface area, fat mass, fat free mass, %fat, waist circumference, waist-to-hip ratio, body weight, and abdominal visceral, subcutaneous, and total fat. Linear mixed models were used to test the association between plasma metabolites and each body composition trait at baseline and in response to training with full covariate adjustment. Significance was set to FDR&lt;0.05. Results: On average, subjects were [mean and (SD)] 35 (14) years old, 33% Black, 54% female, and had BMI of 26.2 (5.2) kg/m 2 . The number of metabolites significantly associated with body composition traits at baseline ranged from 57-141 ( Table 1 ). DMGV was among the top 3 associated metabolites at baseline for all 11 traits, while SM(d18:1/16:1) was associated with 8 of 11 baseline traits. Few if any significant associations were found between change in metabolites and change in body composition measures in response to exercise training (range: 0-10) ( Table 1 ). CONCLUSIONS: Although numerous metabolites were associated with body composition traits at baseline, few associations were observed with trait responses to training. These results suggest that intrinsic body composition and its response to exercise training may have differing underlying metabolic signatures.
Intratumoral dendritic cell–CD4+ T helper cell niches enable CD8+ T cell differentiation following PD-1 blockade in hepatocellular carcinoma
Authors: Assaf Magen, Pauline Hamon, Nathalie Fiaschi, Brian Y. Soong, Matthew D. Park, Raphaël Mattiuz, Etienne Humblin, Leanna Troncoso, Darwin D’souza, Travis Dawson, Joel Kim, Steven Hamel, Mark Buckup, Christie Chang, Alexandra Tabachnikova, Hara Schwartz, Nausicaa Malissen, Yonit Lavin, Alessandra Soares-Schanoski, Bruno Giotti, Samarth Hegde, Giorgio Ioannou, Edgar Gonzalez-Kozlova, Clotilde Hennequin, Jessica Le Berichel, Zhen Zhao, Stephen C. Ward, Isabel Fiel, Baijun Kou, Michael Dobosz, Lianjie Li, Christina Adler, Min Ni, Yi Wei, Wei Wang, Gurinder S. Atwal, Kunal Kundu, Kamil J. Cygan, Alexander M. Tsankov, Adeeb Rahman, Colles Price, Nicolas Fernandez, Jiang He, Namita T. Gupta, Seunghee Kim-Schulze, Sacha Gnjatic, Ephraim Kenigsberg, Raquel P. Deering, Myron Schwartz, Thomas U. Marron, Gavin Thurston, Alice O. Kamphorst, Miriam Merad
Journal: Nature Medicine (2023)
The NCI-MATCH trial: lessons for precision oncology
Authors: Peter J. O’Dwyer, Robert J. Gray, Keith T. Flaherty, Alice P. Chen, Shuli Li, Victoria Wang, Lisa M. McShane, David R. Patton, James V. Tricoli, P. Mickey Williams, A. John Iafrate, Jeffrey Sklar, Edith P. Mitchell, Naoko Takebe, David J. Sims, Brent Coffey, Tony Fu, Mark Routbort, Larry V. Rubinstein, Richard F. Little, Carlos L. Arteaga, Donna Marinucci, Stanley R. Hamilton, Barbara A. Conley, Lyndsay N. Harris, James H. Doroshow
Journal: Nature Medicine (2023)
Abstract 13093: Global Longitudinal Strain Prediction of Cardiac Dysfunction in Hematopoietic Stem Cell Transplant Patients
Authors: Wei-wen Lin, Chieh-Lin, Jerry Teng, Chia-CHi Liu, Wen-Lieng Lee
Journal: Circulation (2022)

Introduction and Hypothesis: Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for hematological malignancies, but patients undergoing HSCT are at increased risk of cardiovascular events and death. Global longitudinal strain (GLS) is more sensitive than left ventricular ejection fraction (LVEF) to identify subclinical LV dysfunction. Early heart failure guideline-directed medical therapy (GDMT) may improve heart function and symptoms in these patients. Methods: Transthoracic echocardiography with speckle tracking was performed every 3 months for 9 months before and after BMT (Figure 1A), with GLS and LVEF as markers of systolic function and E/e' as markers of diastolic function, troponin I, NT-ProBNP and D-dimer as markers of cardiac insufficiency. Patients with a 10% reduction in GLS or a 15% reduction in LVEF from baseline were defined as LV dysfunction and GDMT were prescribed. Results: A total of 27acute myeloid leukemia and 5 acute lymphoblastic leukemia received high dose cyclophosphamide before HSCT, 2 patients developed minimal pericardial effusion without tamponade, 2 patients expired during transplantation. The mean GLS before HSCT was -16.8±0.75%, which was significantly reduced to -15.11±0.86% (p=0.026) after 3 months (Figure 1B). After GDMT, GLS improved to -18.86±1.6% 9 months after HSCT. No significant changes in LVEF, E/e' and serum biomarkers during follow-up Conclusions: Our results further support an increased risk of subclinical myocardial dysfunction in patients with hematological malignancies on HSCT. In these patients, GLS may be an earlier noninvasive marker than LVEF, ECG, or serum biomarkers. Early heart failure GDMT may improve heart function once GLS is reduced.
Intradermal skin test with mRNA vaccines as a surrogate marker of T cell immunity in immunocompromised patients
Authors: Benedict Fallet, Mathilde Foglierini, Raphael Porret, Ana Alcaraz-Serna, Christophe Sauvage, Raphael Jenelten, Teofila Caplanusi, Michel Gilliet, Laurent Perez, Craig Fenwick, Raphael Genolet, Alexandre Harari, Sara Bobisse, Raphael Gottardo, Giuseppe Pantaleo, Yannick D. Muller
Journal: Journal of Infection (2023)

ObjectivesIntradermal skin test (IDT) with mRNA vaccines may represent a simple, reliable, and affordable tool to measure T cell response in immunocompromised patients who failed to mount serological responses following vaccination with mRNA covid-19 vaccines.MethodsWe compared anti-SARS-CoV-2 antibodies and cellular responses in vaccinated immunocompromised patients (n = 58), healthy seronegative naive controls (NC, n = 8), and healthy seropositive vaccinated controls (VC, n = 32) by Luminex, spike-induced IFN-γ Elispot and an IDT. A skin biopsy 24 h after IDT and single-cell RNAseq was performed in three vaccinated volunteers.ResultsTwenty-five percent of seronegative NC had a positive Elispot (2/8) and IDT (1/4), compared to 95% (20/21) and 93% (28/30) in seropositive VC, respectively. Single-cell RNAseq data in the skin of VC showed a predominant mixed population of effector helper and cytotoxic T cells. The TCR repertoire revealed 18/1064 clonotypes with known specificities against SARS-CoV-2, among which six were spike-specific. Seronegative immunocompromised patients with positive Elispot and IDT were in 83% (5/6) treated with B cell-depleting reagents, while those with negative IDT were all transplant recipients.ConclusionsOur results indicate that delayed local reaction to IDT reflects vaccine-induced T-cell immunity opening new perspectives to monitor seronegative patients and elderly populations with waning immunity.
Abstract 11976: Functional Characterization of Calcium Handling Kinetics in Patient-Derived Ipsc-Cm Models of Pkp2-Mediated Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Samantha K Hamrick, CS John Kim, Martina Gluscevic, David J Tester, Michael J Ackerman
Journal: Circulation (2022)

Introduction: Pathogenic variants in PKP2 -encoded plakophilin 2 cause arrhythmogenic right ventricular cardiomyopathy (ARVC). Electrocardiographically, PKP2 -mediated ARVC may mimic RYR2 -mediated catecholaminergic polymorphic ventricular tachycardia (CPVT). We compare the underlying mechanism of arrhythmia in ARVC and CPVT using induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Methods: iPSC-CMs were generated from 2 ARVC patients with different PKP2 variants [E149X (PKP2-1) and c.2146-1G&gt;C (PKP2-2)], 1 patient with a CPVT variant [RyR2-R176Q (CPVT1)], and a wild-type (WT) control. Fluo-4 AM calcium dye was used to assess calcium kinetics in iPSC-CMs before and during treatment with 100 nM isoproterenol (ISO) at 8-10 min. Results: Compared to WT, PKP2 and RYR2 iPSC-CMs had a greater amplitude before (WT: 0.331±0.031, PKP2-1: 1.048±0.074, PKP2-2: 1.076±0.095, CPVT1: 0.966±0.061; P&lt;0.0001) and during ISO (WT: 0.277±0.022, PKP2-1: 0.971±0.069, PKP2-2: 0.622±0.041, CPVT1: 0.756±0.051; P&lt;0.0001). The Ca 2+ transient duration (CTD100) was longer in PKP2 and RYR2 iPSC-CMs compared to WT before (WT: 1.01±0.05 s, PKP2-1: 1.84±0.01 s, PKP2-2: 1.76±0.02 s, CPVT1: 1.81±0.02 s; P&lt;0.0001) and during ISO (WT: 1.38±0.05 s, PKP2-1: 1.65±0.03 s, PKP2-2: 1.71±0.03 s, CPVT1: 1.61±0.05 s; P&lt;0.001). Before (WT: 259±13 ms, PKP2-1: 538±23 ms, PKP2-2: 493±28 ms, CPVT1: 586±24 ms; P&lt;0.0001) and during ISO (WT: 311±19 ms, PKP2-1: 406±21 ms, P=0.0172, PKP2-2: 487±28 ms, P&lt;0.0001, CPVT1: 453±21 ms, P=0.0001), peak to 50% decay time was slower in PKP2 and RYR2 iPSC-CMs compared with WT. Upstroke time was longer in PKP2 and RYR2 iPSC-CMs compared to WT before (WT: 205±5 ms, PKP2-1: 539±13 ms, PKP2-2: 429±19 ms, CPVT1: 455±12 ms; P&lt;0.0001) and during ISO (WT: 213±7 ms, PKP2-1: 375±16 ms, PKP2-2: 416±20 ms, CPVT1: 389±10 ms; P&lt;0.0001). Conclusion: Here, iPSC-CMs, derived from patients with either PKP2 -mediated ARVC or RYR2 -mediated CPVT, display similar abnormal calcium handling properties such as greater amplitude, longer CTD100, and slower peak to 50% decay time and upstroke time compared to WT iPSC-CMs before and during ISO treatment. This may explain why patients with PKP2 -mediated ARVC often mimic the treadmill stress test seen in patients with CPVT1.
Abstract 12037: Tricuspid Annular Area and Leaflets Stretch Are Associated With Functional Tricuspid Regurgitation - Insights From Three-Dimensional Transesophageal Echocardiography
Authors: Mana Ogawa, asahiro ito, Ayaka Ito, Andrew T Kim, Sera Ishikawa, Shinichi Iwata, Yosuke Takahashi, Yasuhiro Izumiya, Toshihiko Shibata, Daiju Fukuda
Journal: Circulation (2022)

Background: The presence of functional tricuspid regurgitation (TR) is associated with mortality and morbidity. Although uniform management with a tricuspid annuloplasty ring is currently considered as a standard surgical procedure, high rates of residual TR despite annuloplasty are reported. Therefore, the identification of the TR mechanisms would be necessary to provide personalized treatment for each TR patient. Methods: This study population consisted of 106 patients with mitral regurgitation (MR) who were scheduled for procedure. Transthoracic and transesophageal echocardiography were performed prior to mitral valve intervention. We performed three-dimensional quantitative assessment including tricuspid annular (TA) area and the distance between the three commissures of tricuspid valve. Results: Moderate or greater TR was detected in 23 (22%). TA area (P &lt; 0.01) and the distance between septum length (SL) (P = 0.02) and posterior length (PL) (p = 0.02) were significantly associated with moderate or greater TR, while TA diameter assessed using trans thoracic echocardiography was not. When patients were divided into four groups according to SL and PL, the group with longer SL and PL had greater risk of moderate or greater TR (P &lt;0.01). Conclusions: Larger TA area and longer SL and PL, which represents limiting the amount of leaflet coaptation resulting from greater stretch of leaflets, are associated with functional TR in in patients with severe MR. The restoration of leaflet coaptation with autologous pericardial patch in addition to tricuspid annuloplasty ring may avoid or delay progression of residual TR and improve prognosis in patients with severe MR.
Abstract 12100: Catastrophic Large Post-Stemi Inferoseptum Ventricular Septal Rupture With Left-to-Right Shunt and an Inferoseptum Pulsatile Pseudoaneurysm
Authors: Alejandro Sanchez-Nadales, Muftawu-Deen Iddrisu, Antonio Lewis, Dipan Uppal, Radhika Neicheril, David Snipelisky, Craig R Asher
Journal: Circulation (2022)

Case Presentation: 49-year-old male without known cardiovascular history presented with three days of atypical chest discomfort. 12-lead EKG revealed ST-segment elevations in II-III-aVF and depression in V1 suggestive of an acute infero-posterior MI (A), Troponin T at 6.85 ng/mL. Following administration of DAPT and heparinization, emergent coronary angiography proved a dominant RCA with proximal 60% and middle 100% occlusion (B), 80% focal stenosis at mid-LAD and 70% focal stenosis at prox-LCx (C). PCI with intra-aortic balloon pump support was performed, with two DES deployed in the RCA, use of a trans-venous pacemaker was required for complete AV block, and two defibrillations required for ventricular fibrillation. Following further hemodynamic compromise unexplained by his hemodynamic parameters, TEE was performed, demonstrating a large mid/distal infero-septum ventricular septal defect with left to right shunt (D, E and F), as well as a basal/mid infero-septum large pseudo-aneurysm (PSA) cavity (contained rupture) (G: low velocity Doppler flow from LV to PSA cavity, H and I show intact septum). The patient continued to decompensate requiring escalation to temporary mechanical circulatory support with VA-ECMO. Heart transplantation was initially considered, family decided to withdraw care due to multi-organ failure and poor prognosis Discussion: Due to widespread availability of primary percutaneous coronary intervention with early reperfusion, mechanical complications post MI are less common in current days. Following transmural MI, persistent hypotension and cardiogenic shock should alert for complications such as VSD or PSA. While VSD may be amenable to percutaneous or surgical closure, PSA is associated with very high mortality even if surgery is attempted. Given the presence of both a VSD and PSA, mechanical support with VA-ECMO allowed us to support the patient for several days as a bridge to decision regarding heart transplantation
Abstract 12115: TAVR Endocarditis Complicated by Aortic Root Pseudoaneurysm
Authors: Solomon Bienstock, Ismail El-Hamamsy, Anna Plitt, Javier Sanz, Gina LaRocca, Annapoorna Kini, Mohamed Al-kazaz
Journal: Circulation (2022)

Case Presentation: An 83-year-old man with hypertension, hyperlipidemia, atrial fibrillation, non-obstructive CAD, and severe AS status post TAVR 4 months prior was transferred from an outside hospital with reported persistent fever for one week. He had no other procedure recently including dental work. He was found to have staphylococcus epidermidis bacteremia in multiple blood cultures. His outside hospital TEE showed pulsatility of the non-coronary sinus with possible vegetations on the noncoronary cusp of the TAVR. On physical examination, he was afebrile, normotensive, and well appearing. His cardiovascular examination, laboratory tests, and chest radiograph were unremarkable, and he denied any chest pain or shortness of breath. His ECG revealed rate-controlled atrial fibrillation. A cardiac CTA revealed a 6 mm mobile hypodense thickening of the non-coronary prosthetic cusp, suspicious for vegetation and a contrast opacifying outpouching in the aortic root near the aorto-mitral curtain, suspicious for pseudoaneurysm. The patient underwent TAVR explantation, pseudoaneurysm exclusion, and AVR using a 23 mm bioprosthesis (Figure). He was discharged 8 days later on antibiotic treatment. At follow-up, the patient felt well with no complaints. Discussion: TAVR endocarditis with resulting aortic root pseudoaneurysm is an immensely rare entity, where there is lack of clinical data with regards to management. Guidelines of prosthetic valve endocarditis (for both TAVR and SAVR) recommend surgical treatment in such cases, although this recommendation was mostly based on the SAVR literature and many patients who undergo TAVR are at higher surgical risk at baseline. Recent studies on TAVR explantation showcase the risky nature of surgery in these patients, with high mortality rates, making treatment decisions less clear. Careful multidisciplinary discussion of risk and benefits is vital to guide clinical decision making in these complex patients.
Abstract 12056: Angiopoietin-Like Protein 3 Blood Levels and Cardiometabolic Traits and Diseases: A Mendelian Randomization Study
Authors: Emilie Gobeil, Jerome Bourgault, Eloi Gagnon, Benoit J Arsenault
Journal: Circulation (2022)

Introduction: Angiopoietin-like 3 (ANGPTL3) is a key regulator of blood lipid levels. ANGPTL3 inhibitors are currently under investigation for their impact on metabolic and cardiovascular health. Our objective was to investigate the causal effect of genetically-predicted blood ANGPTL3 levels on cardiometabolic traits and diseases using Mendelian randomization (MR). Methods: We performed a series of two-sample MR studies using cis-acting variants on ANGPTL3 blood levels measured using aptamers in 35,559 participants of the deCODE study. We used inverse-variance weighted-MR to assess the effect of genetically-predicted blood ANGPTL3 levels on lipid and apolipoprotein B levels (from the UK Biobank, n = 441,016 participants), non-alcoholic fatty liver disease (from a genome-wide association meta-analysis [GWAS] of 8434 cases and 770,614 controls of European ancestry), type 2 diabetes (from the DIAGRAM consortium, 74,124 cases and 824,006 controls), acute pancreatitis (from a GWAS of 7832 cases and 793,427 controls of European ancestry) and coronary artery disease (from the CARDIoGRAMplusC4D and UK Biobank GWAS meta-analysis [34,541 cases and 261,984 controls of European ancestry]). Results: We selected 27 independent variants near or in the ANGPTL3 region associated with ANGPTL3 blood levels (R2&lt;0.1, p&lt;5x10 -08 ). Genetically-predicted ANGPTL3 levels were strongly and significantly associated with triglyceride and apolipoprotein B levels (beta [SE] = 0.156 [0.032], p-value = 1.05x10 -06 , and beta [SE] = 0.058 [0.013], p-value = 8.16x10 -06 , respectively) but were not associated with non-alcoholic fatty liver disease, type 2 diabetes or coronary artery disease (all p-values &gt; 0.05). Genetically-predicted ANGPTL3 levels were however significantly associated with acute pancreatitis (beta [SE] = 0.071 [0.025], and p-value = 0.004). Conclusions: Our two-sample MR study revealed that blood ANGPTL3 levels may be causally-related to lipid-lipoprotein levels, but not with cardiometabolic diseases. Blood ANGPTL3 levels were however associated with acute pancreatitis, thereby suggesting that ANGPTL3 inhibition might warrant further investigation in the prevention of acute pancreatitis.
Surgical intervention as a driver of new angiogenesis in tumors—time to consider minimally invasive surgeries?
Authors: Vimalraj Selvaraj, Saravanan Sekaran, Sureh Kumar Rajamani Sekar
Journal: International Journal of Surgery (2023)

aDepartment of Prosthodontics, Saveetha Dental College and Hospitals, Saveetha Institute for Medical and Technical Sciences, Chennai-600077, Tamil Nadu, India bCollege of Natural Sciences, Arba Minch University, SNNPR, Ethiopia Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Assistant Professor, Department of Prosthodontics, Saveetha Dental College and Hospitals, Saveetha Institute for Medical and Technical Sciences, Chennai-600077, Tamil Nadu, India. E-mail address: [email protected] (S. Sekaran). *Corresponding author. Address: Professor, Department of Prosthodontics, Saveetha Dental College and Hospitals, Saveetha Institute for Medical and Technical Sciences, Chennai-600077, Tamil Nadu, India. E-mail address: [email protected] (V. Selvaraj). *Corresponding author. Address: Assistant Professor, College of Natural Sciences, Arba Minch University, SNNPR, Ethiopia, 4400. E-mail address: [email protected] (S.K. Rajamani Sekar). This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-nc-sa/4.0/
Abstract 11905: Dexmedetomidine for Sedation During Epicardial Ablation for Ventricular Tachycardia: A Single-Center Experience
Authors: Sergio Conti, Francesco Sabatino, Giuseppe Sgarito
Journal: Circulation (2022)

Introduction: Epicardial ablation of ventricular tachycardia (VT) is mainly performed under general anesthesia (GA). However, GA lowers blood pressure, may interfere with arrhythmia induction, and the use of muscle relaxants precludes identification of the phrenic nerve. Moreover, an anesthesiologist's is required during GA for the whole procedure, which may not always be possible. Hypothesis: The aim of there study was to evaluate the feasibility and safety of epicardial VT ablations under conscious sedation using dexmedetomidine. Methods: Between 2018 and 2022, all patients who underwent epicardial VT ablation under dexmedetomidine infusion were prospectively enrolled. All patients received premedication with paracetamol 1 g (acetaminophen 10 mg/ml) and ketorolac 30 mg. Sedation protocol included an i.v. bolus of midazolam (0.03-0.05 mg/kg) followed by continuous infusion of dexmedetomidine (0.2-0.7 mcg/kg/h). In addition, an i.v. fentanyl bolus (0.7-1.4 mcg/kg) was given for short-term analgesia, followed by a second dose after 30-45 minutes. Sedation-related complications were: hypoxia (S02&lt;90%), severe hypotension (MAP&lt;60 mmHg), and bradycardia (HR &lt;45 b/m). Results: Seventy-one patients with drug-refractory recurrent VT underwent epicardial or endo-epi ablation under conscious sedation. Standard percutaneous sub-xiphoid access was attempted in all patients. in 2 patients the procedure was switched to GA because of intractable pain during epicardial catheter's manipulation. Data from 69 patients were analyzed. Mean age was 65.4±12.1 years and 66.6% of patients were males. Forty-seven patients (68.1%) had non-ischemic cardiomyopathy, 13 patients (18.9%) had ischemic-cardiomyopathy, and 9 patients (13%) had myocarditis. Procedural-related complications occurred in five patients (7.2%), one transient phrenic nerve palsy, two pericarditis, and two vascular complications. No severe adverse events related to the sedation occurred. Conclusions: Prompt availability of anesthesia support remains crucial for epicardial VT ablation. Continuous infusion of dexmedetomidine in addition to midazolam and fentanyl seems to be a safe and effective sedation protocol in patients undergoing epicardial VT ablation.